Toll-like receptors (TLRs) are sensors in the activation of innate immune cells including monocytes, macrophages and dendritic cells. These cells function as sentinels against foreign antigens and pathogens, recognizing pathogen-associated molecular patterns (PAMPs) through pattern-recognition receptors (PRRs). Activation of PRRs initiate an array of innate immune responses, which serve to augment subsequent adaptive immune responses. The ten functional TLRs in the human encode proteins with an extracellular domain having leucine-rich repeats (LRR) and a cytosolic domain called the Toll/IL-1 receptor (TIR) domain. TLR1, -2, -4, -5, and -6 recognize extracellular stimuli, while TLR3, -7, -8 and -9 function within the endolysosomal compartment. The ligands for TLRs are highly conserved molecules such as lipopolysaccharides (LPS) and monophosphoryl lipid A (MPLA) (recognized by TLR4), lipopeptides (TLR2 in combination with TLR1 or TLR6), flagellin (TLR5), single stranded RNA (TLR7 and TLR8), double stranded RNA (TLR3), and CpG motif-containing DNA (recognized by TLR9).
T lymphocytes bear antigen specific receptors on their cell surface to allow recognition of foreign pathogens, and their effector functions are determined in part by the production of key cytokines. The two main subsets of T lymphocytes are distinguished by cell surface markers Cluster of Differentiation 4 (CD4) and CD8. CD4-expressing helper T lymphocytes are prolific cytokine producers and can be further subdivided into Th1 and Th2 subsets, depending on specific cytokine signatures. In the context of Th1-biased adaptive immune responses, TLR8 is of particular significance. The engagement of TLR8, which is expressed predominantly in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells, potently enhances the production of Th1-polarizing cytokines, tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), IL-18, and interferon-γ (IFN-γ).